Abstract
Two ubiquitous calpains (extremely calcium-dependent, neutral, cytoplasmic cysteine proteases) and their endogenous inhibitor – calpastatin – form the calpain-calpastatin system (CCS). Activity of the CCS is implicated in the processes of proliferation and apoptosis of many human cell types. We have demonstrated a necessity of resting activity of the CCS for adequate proliferative response of nonmalignant T lymphocytes, as well as the reduction of amounts and activities of the CCS proteases in the elderly. On the other hand, we have also shown that hyperactivity of the CCS protects chronic B-cell leukemia (B-CLL) cells from apoptosis and possibly induces their excessive proliferation. As the B-CLL is the typical leukemia of old age, and relatively frequently transforms into the tumor (lymphoma) growth, it was interesting to analyze the existing data on overall role of the CCS in the processes of proliferation, apoptosis, aging, and malignant transformation of human lymphoid cells. This chapter summarizes these data.
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References
Anding AL, Baehrecke EH. Cleaning house: selective autophagy of organelles. Dev Cell. 2017;41:10–22. https://doi.org/10.1016/j.devcel.2017.02.016.
Baird S. The usefulness of cell surface markers in predicting the prognosis of non-Hodgkin’s lymphomas. Crit Rev Clin Lab Sci. 1993;30:1–28. https://doi.org/10.3109/10408369309084664.
Baudry M, Bi X. Calpain-1 and Calpain-2: The Yin and Yang of synaptic plasticity and neurodegeneration. Trends Neurosci. 2016;39:235–45. https://doi.org/10.1016/j.tins.2016.01.007.
Boyd RS, Jukes-Jones R, Walewska R, Brown D, Dyer MJ, Cain K. Protein profiling of plasma membranes defines aberrant signaling pathways in mantle cell lymphoma. Mol Cell Proteomics. 2009;8:1501–15. https://doi.org/10.1074/mcp.M800515-MCP200.
Brower CS, Piatkov KI, Varshavsky A. Neurodegeneration-associated protein fragments as short-lived substrates of the N-end rule pathway. Mol Cell. 2013;50:161–71. https://doi.org/10.1016/j.molcel.2013.02.009.
Caporaso NE, Goldin LR, Anderson WF, Landgren O. Current insight on trends, causes, and mechanisms of Hodgkin’s lymphoma. Cancer J. 2009;15:117–23. https://doi.org/10.1097/PPO.0b013e3181a39585.
Carragher NO, Fonseca BD, Frame MC. Calpain activity is generally elevated during transformation but has oncogene-specific biological functions. Neoplasia. 2004;6:53–73.
Choi YH, Lee SJ, Nguyen P, Jang JS, Lee J, Wu ML, Takano E, Maki M, Henkart PA, Trepel JB. Regulation of cyclin D1 by calpain protease. J Biol Chem. 1997;272:28479–84.
Conacci-Sorrell M, Eisenman RN. Post-translational control of Myc function during differentiation. Cell Cycle. 2011;10:604–10. https://doi.org/10.4161/cc.10.4.14794.
Conacci-Sorrell M, Ngouenet C, Eisenman RN. Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation. Cell. 2010;142:480–93. https://doi.org/10.1016/j.cell.2010.06.037.
Conacci-Sorrell M, Ngouenet C, Anderson S, Brabletz T, Eisenman RN. Stress-induced cleavage of Myc promotes cancer cell survival. Genes Dev. 2014;28:689–707. https://doi.org/10.1101/gad.231894.113.
Cooperman J, Neely R, Teachey DT, Grupp S, Choi JK. Cell division rates of primary human precursor B cells in culture reflect in vivo rates. Stem Cells. 2004;22:1111–20. https://doi.org/10.1634/stemcells.22-6-1111.
Dadi S, Le Noir S, Payet-Bornet D, Lhermitte L, Zacarias-Cabeza J, Bergeron J, Villarese P, Vachez E, Dik WA, Millien C, Radford I, Verhoeyen E, Cosset FL, et al. TLX homeodomain oncogenes mediate T cell maturation arrest in T-ALL via interaction with ETS1 and suppression of TCR alpha gene expression. Cancer Cell. 2012;21:563–76. https://doi.org/10.1016/j.ccr.2012.02.013.
Dho SH, Deverman BE, Lapid C, Manson SR, Gan L, Riehm JJ, Aurora R, Kwon KS, Weintraub SJ. Control of cellular Bcl-xL levels by deamidation-regulated degradation. PLoS Biol. 2013;11:e1001588. https://doi.org/10.1371/journal.pbio.1001588.
DuVerle DA, Ono Y, Sorimachi H, Mamitsuka H. Calpain cleavage prediction using multiple kernel learning. PLoS One. 2011;6:e19035. https://doi.org/10.1371/journal.pone.0019035.
Fisher SG, Fisher RI. The epidemiology of non-Hodgkin’s lymphoma. Oncogene. 2004;23:6524–34. https://doi.org/10.1038/sj.onc.1207843.
Franco SJ, Huttenlocher A. Regulating cell migration: calpains make the cut. J Cell Sci. 2005;118:3829–38. https://doi.org/10.1242/jcs.02562.
Friedrich P, Bozoky Z. Digestive versus regulatory proteases: on calpain action in vivo. Biol Chem. 2005;386:609–12. https://doi.org/10.1515/BC.2005.071.
Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003;83:731–801. https://doi.org/10.1152/physrev.00029.2002.
Hendry L, John S. Regulation of STAT signalling by proteolytic processing. Eur J Biochem. 2004;271:4613–20. EJB4424 [pii]. https://doi.org/10.1111/j.1432-1033.2004.04424.x.
Ishihara M, Araya N, Sato T, Tatsuguchi A, Saichi N, Utsunomiya A, Nakamura Y, Nakagawa H, Yamano Y, Ueda K. Preapoptotic protease calpain-2 is frequently suppressed in adult T-cell leukemia. Blood. 2013;121:4340–7. https://doi.org/10.1182/blood-2012-08-446922.
Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, Ikeda Y, Kizaki M. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004;64:1071–8.
Kunkalla K, Liu Y, Qu C, Leventaki V, Agarwal NK, Singh RR, Vega F. Functional inhibition of BCL2 is needed to increase the susceptibility to apoptosis to SMO inhibitors in diffuse large B-cell lymphoma of germinal center subtype. Ann Hematol. 2013;92:777–87. https://doi.org/10.1007/s00277-013-1684-6.
Lang W, Kienzle S, Diehl V. Proliferation kinetics of malignant non-Hodgkin’s lymphomas related to histopathology of lymph node biopsies. Virchows Arch A Pathol Anat Histol. 1980;389:397–407.
Li H, Nepal RM, Martin A, Berger SA. Induction of apoptosis in Emu-myc lymphoma cells in vitro and in vivo through calpain inhibition. Exp Hematol. 2012;40:548–63 e2. https://doi.org/10.1016/j.exphem.2012.02.002.
Lopatniuk P, Witkowski JM. Conventional calpains and programmed cell death. Acta Biochim Pol. 2011;58:287–96.
Mani H, Jaffe ES. Hodgkin lymphoma: an update on its biology with new insights into classification. Clin Lymphoma Myeloma. 2009;9:206–16. https://doi.org/10.3816/CLM.2009.n.042.
McCarthy MK, Weinberg JB. The immunoproteasome and viral infection: a complex regulator of inflammation. Front Microbiol. 2015;6:21. https://doi.org/10.3389/fmicb.2015.00021.
Mikosik A, Zaremba A, Puchalska Z, Daca A, Smolenska Z, Lopatniuk P, Mital A, Hellman A, Bryl E, Witkowski JM. Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation. Folia Histochem Cytobiol. 2007;45:343–7.
Mikosik A, Foerster J, Jasiulewicz A, Frackowiak J, Colonna-Romano G, Bulati M, Buffa S, Martorana A, Caruso C, Bryl E, Witkowski JM. Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project. Immun Ageing. 2013;10:27. https://doi.org/10.1186/1742-4933-10-27.
Mikosik A, Henc I, Ruckemann-Dziurdzinska K, Frackowiak JE, Ploszynska A, Balcerska A, Bryl E, Witkowski JM. Increased mu-Calpain activity in blasts of common B-precursor childhood acute lymphoblastic leukemia correlates with their lower susceptibility to apoptosis. PLoS One. 2015;10:e0136615. https://doi.org/10.1371/journal.pone.0136615. [doi] PONE-D-13-51200 [pii]
Mikosik A, Jasiulewicz A, Daca A, Henc I, Frackowiak JE, Ruckemann-Dziurdzinska K, Foerster J, Le Page A, Bryl E, Fulop T, Witkowski JM. Roles of calpain-calpastatin system (CCS) in human T cell activation. Oncotarget. 2016;7:76479–95. https://doi.org/10.18632/oncotarget.13259.
Mitchell TJ, John S. Signal transducer and activator of transcription (STAT) signalling and T-cell lymphomas. Immunology. 2005;114:301–12. https://doi.org/10.1111/j.1365-2567.2005.02091.x.
Moretti D, Del Bello B, Allavena G, Maellaro E. Calpains and cancer: friends or enemies? Arch Biochem Biophys. 2014;564:26–36. https://doi.org/10.1016/j.abb.2014.09.018.
Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11:823–36. https://doi.org/10.1038/nri3084.
Nixon RA. The calpains in aging and aging-related diseases. Ageing Res Rev. 2003;2:407–18.
Oda A, Wakao H, Fujita H. Calpain is a signal transducer and activator of transcription (STAT) 3 and STAT5 protease. Blood. 2002;99:1850–2.
Ono Y, Sorimachi H. Calpains: an elaborate proteolytic system. Biochim Biophys Acta. 1824;2012:224–36. https://doi.org/10.1016/j.bbapap.2011.08.005.
Ono Y, Saido TC, Sorimachi H. Calpain research for drug discovery: challenges and potential. Nat Rev Drug Discov. 2016;15:854–76. https://doi.org/10.1038/nrd.2016.212.
Packham G, Krysov S, Allen A, Savelyeva N, Steele AJ, Forconi F, Stevenson FK. The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy. Haematologica. 2014;99:1138–48. https://doi.org/10.3324/haematol.2013.098384.
Perrin BJ, Huttenlocher A. Calpain. Int J Biochem Cell Biol. 2002;34:722–5.
Piatkov KI, Brower CS, Varshavsky A. The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments. Proc Natl Acad Sci U S A. 2012;109:E1839–47. https://doi.org/10.1073/pnas.1207786109.
Piatkov KI, Oh J-H, Liu Y, Varshavsky A. Calpain-generated natural protein fragments as short-lived substrates of the N-end rule pathway. Proc Natl Acad Sci. 2014;111:E817–E26. https://doi.org/10.1073/pnas.1401639111.
Pinto JR, Muller-Delp J, Chase PB. Will you still need me (Ca2+, TnT, and DHPR), will you still cleave me (calpain), when I’m 64? Aging Cell. 2017;16:202–4. https://doi.org/10.1111/acel.12560.
Potz BA, Abid MR, Sellke FW. Role of calpain in pathogenesis of human disease processes. J Nat Sci. 2016;2:e218.
Rao H, Uhlmann F, Nasmyth K, Varshavsky A. Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature. 2001;410:955–9. https://doi.org/10.1038/35073627.
Ruiz-Vela A, Gonzalez de Buitrago G, Martinez AC. Implication of calpain in caspase activation during B cell clonal deletion. EMBO J. 1999;18:4988–98. https://doi.org/10.1093/emboj/18.18.4988.
Saido TC, Shibata M, Takenawa T, Murofushi H, Suzuki K. Positive regulation of mu-calpain action by polyphosphoinositides. J Biol Chem. 1992;267:24585–90.
Saido TC, Sorimachi H, Suzuki K. Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J. 1994;8:814–22.
Sarin A, Clerici M, Blatt SP, Hendrix CW, Shearer GM, Henkart PA. Inhibition of activation-induced programmed cell death and restoration of defective immune responses of HIV+ donors by cysteine protease inhibitors. J Immunol. 1994;153:862–72.
Sessoms JS, Chen SJ, Chetkovich DM, Powell CM, Roberson ED, Sweatt JD, Klann E. Ca(2+)-induced persistent protein kinase C activation in rat hippocampal homogenates. Second Messengers Phosphoproteins. 1992;14:109–26.
Shi M, Zhang T, Sun L, Luo Y, Liu DH, Xie ST, Song XY, Wang GF, Chen XL, Zhou BC, Zhang YZ. Calpain, Atg5 and Bak play important roles in the crosstalk between apoptosis and autophagy induced by influx of extracellular calcium. Apoptosis. 2013;18:435–51. https://doi.org/10.1007/s10495-012-0786-2.
Shumway SD, Miyamoto S. A mechanistic insight into a proteasome-independent constitutive inhibitor kappaBalpha (IkappaBalpha) degradation and nuclear factor kappaB (NF-kappaB) activation pathway in WEHI-231 B-cells. Biochem J. 2004;380:173–80. https://doi.org/10.1042/BJ20031796.
Shumway SD, Maki M, Miyamoto S. The PEST domain of IkappaBalpha is necessary and sufficient for in vitro degradation by mu-calpain. J Biol Chem. 1999;274:30874–81.
Small GW, Chou TY, Dang CV, Orlowski RZ. Evidence for involvement of calpain in c-Myc proteolysis in vivo. Arch Biochem Biophys. 2002;400:151–61. https://doi.org/10.1016/S0003-9861(02)00005-X.
Smedby KE, Hjalgrim H. Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Cancer Biol. 2011;21:293–8. https://doi.org/10.1016/j.semcancer.2011.09.010.
Sorimachi H, Ono Y. Regulation and physiological roles of the calpain system in muscular disorders. Cardiovasc Res. 2012;96:11–22. https://doi.org/10.1093/cvr/cvs157.
Sorimachi H, Mamitsuka H, Ono Y. Understanding the substrate specificity of conventional calpains. Biol Chem. 2012;393:853–71. https://doi.org/10.1515/hsz-2012-0143.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90. https://doi.org/10.1182/blood-2016-01-643569.
Tacke F, Marini FC 3rd, Zhao S, McQueen T, Konopleva M, Ruvolo PP, Hu SX, Xu HJ, Andreeff M. Expression of inducible Bcl-X(S) in myeloid leukemia: compensatory upregulation of Bcl-X(L) and Bcl-2 prevents apoptosis and chemosensitization. Cancer Biol Ther. 2004;3:340–7.
Tan Y, Wu C, De Veyra T, Greer PA. Ubiquitous calpains promote both apoptosis and survival signals in response to different cell death stimuli. J Biol Chem. 2006;281:17689–98. https://doi.org/10.1074/jbc.M601978200.
Tompa P, Emori Y, Sorimachi H, Suzuki K, Friedrich P. Domain III of calpain is a ca2+-regulated phospholipid-binding domain. Biochem Biophys Res Commun. 2001;280:1333–9. https://doi.org/10.1006/bbrc.2001.4279.
Tompa P, Buzder-Lantos P, Tantos A, Farkas A, Szilagyi A, Banoczi Z, Hudecz F, Friedrich P. On the sequential determinants of calpain cleavage. J Biol Chem. 2004;279:20775–85. https://doi.org/10.1074/jbc.M313873200.
Varshavsky A. Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis. Protein Sci. 2012;21:1634–61. https://doi.org/10.1002/pro.2148.
Wendt A, Thompson VF, Goll DE. Interaction of calpastatin with calpain: a review. Biol Chem. 2004;385:465–72. https://doi.org/10.1515/BC.2004.054.
Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A, Pask D, Goldsmith P, O’Kane CJ, Floto RA, Rubinsztein DC. Novel targets for Huntington’s disease in an mTOR-independent autophagy pathway. Nat Chem Biol. 2008;4:295–305. https://doi.org/10.1038/nchembio.79.
Witkowski JM, Zmuda-Trzebiatowska E, Swiercz JM, Cichorek M, Ciepluch H, Lewandowski K, Bryl E, Hellmann A. Modulation of the activity of calcium-activated neutral proteases (calpains) in chronic lymphocytic leukemia (B-CLL) cells. Blood. 2002;100:1802–9. https://doi.org/10.1182/blood-2001-11-0073.
Zhang Q, Nowak I, Vonderheid EC, Rook AH, Kadin ME, Nowell PC, Shaw LM, Wasik MA. Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome. Proc Natl Acad Sci U S A. 1996;93:9148–53.
Zhu DM, Uckun FM. Calpain inhibitor II induces caspase-dependent apoptosis in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells as well as some solid tumor cells. Clin Cancer Res. 2000;6:2456–63.
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Witkowski, J.M., Mikosik, A., Bryl, E., Fulop, T. (2018). Calpain-Calpastatin System in Lymphoid Neoplasm of the Aged. In: Extermann, M. (eds) Geriatric Oncology . Springer, Cham. https://doi.org/10.1007/978-3-319-44870-1_70-1
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